Proteoglycans and their roles in brain cancer

Authors

  • Anna Wade,

    1. Department of Neurological Surgery, UCSF, San Francisco, CA, USA
    2. Brain Tumor Research Center, UCSF, San Francisco, CA, USA
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  • Aaron E. Robinson,

    1. Department of Neurological Surgery, UCSF, San Francisco, CA, USA
    2. Brain Tumor Research Center, UCSF, San Francisco, CA, USA
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  • Jane R. Engler,

    1. Department of Neurological Surgery, UCSF, San Francisco, CA, USA
    2. Brain Tumor Research Center, UCSF, San Francisco, CA, USA
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  • Claudia Petritsch,

    1. Department of Neurological Surgery, UCSF, San Francisco, CA, USA
    2. Brain Tumor Research Center, UCSF, San Francisco, CA, USA
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  • C. David James,

    1. Department of Neurological Surgery, UCSF, San Francisco, CA, USA
    2. Brain Tumor Research Center, UCSF, San Francisco, CA, USA
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  • Joanna J. Phillips

    Corresponding author
    1. Brain Tumor Research Center, UCSF, San Francisco, CA, USA
    2. Neuropathology, Department of Pathology, UCSF, San Francisco, CA, USA
    • Department of Neurological Surgery, UCSF, San Francisco, CA, USA
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Correspondence

J. J. Phillips, Departments of Neurological Surgery and Pathology, 1450 Third Street, HD281, Box 0520, University of California San Francisco, San Francisco, CA 94158, USA

Fax: +1 415 514 9729

Tel: +1 415 514 4929

E-mail: joanna.phillips@ucsf.edu

Abstract

Glioblastoma, a malignant brain cancer, is characterized by abnormal activation of receptor tyrosine kinase signalling pathways and a poor prognosis. Extracellular proteoglycans, including heparan sulfate and chondroitin sulfate, play critical roles in the regulation of cell signalling and migration via interactions with extracellular ligands, growth factor receptors and extracellular matrix components, as well as intracellular enzymes and structural proteins. In cancer, proteoglycans help drive multiple oncogenic pathways in tumour cells and promote critical tumour–microenvironment interactions. In the present review, we summarize the evidence for proteoglycan function in gliomagenesis and examine the expression of proteoglycans and their modifying enzymes in human glioblastoma using data obtained from The Cancer Genome Atlas (http://cancergenome.nih.gov/). Furthermore, we demonstrate an association between specific proteoglycan alterations and changes in receptor tyrosine kinases. Based on these data, we propose a model in which proteoglycans and their modifying enzymes promote receptor tyrosine kinase signalling and progression in glioblastoma, and we suggest that cancer-associated proteoglycans are promising biomarkers for disease and therapeutic targets.

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